Non-thiazolidinedione antihyperglycaemic agents. Part 3: The effects of stereochemistry on the potency of alpha-methoxy-beta-phenylpropanoic acids.

Rhizopus delemar lipase catalysed ester hydrolysis of the alpha-methoxy-beta-phenylpropanoate 1 affords the (R)-(+) and (S)-(-) isomers in > 84% enantiomeric excess. Absolute stereochemistry was determined by a single crystal X-ray analysis of a related synthetic analogue. The activity of these two enantiomers on glucose transport in vitro and as anti-diabetic agents in vivo is reported and their unexpected equivalence attributed to an enzyme-mediated stereospecific isomerisation of the (R)-(+) isomer. Binding studies using recombinant human PPARgamma (peroxisomal proliferator activated receptor gamma), now established as a molecular target for this compound class, indicate a 20-fold higher binding affinity for the (S) antipode relative to the (R) antipode.     

Imitator strategies

An imitator strategy in an evolutionary game is a pair (u, p) consisting of a conventional and generally-known strategy u (the personal strategy) and a probability p of using the opponent's personal strategy rather than one's own. The question of whether imitator strategies (p > 0) can be used to invade populations using conventional ESSs is explored, and is found to depend in part on the variability of strategy present in the initial population. Interior values of p (0 < p < 1) are found never to be optimal. Examples are used repeatedly to illustrate the theory. The imitator strategy is also compared with the successful Tit-for-Tat strategy considered in the Axelrod-Hamilton study of the Prisoner's dilemma.     

Microbial endocrinology: how stress influences susceptibility to infection

A holistic approach to understanding the mechanisms by which stress influences the pathogenesis of infectious disease has resulted in the development of the field of microbial endocrinology. This transdisciplinary field represents the intersection of microbiology with mammalian endocrinology and neurophysiology, and is based on the tenet that microorganisms have evolved systems for using neurohormones, which are widely distributed throughout nature, as environmental cues to initiate growth and pathogenic processes. This review reveals that responsiveness to human stress hormones is widespread in the microbial world and documents recent advances in microbial endocrinology.     

The BPI-like/PLUNC family proteins in cattle

Members of the protein family having similarity to BPI (bactericidal/permeability increasing protein) (the BPI-like proteins), also known as the PLUNC (palate, lung and nasal epithelium clone) family, have been found in a range of mammals; however, those in species other than human or mouse have been relatively little characterized. Analysis of the BPI-like proteins in cattle presents unique opportunities to investigate the function of these proteins, as well as address their evolution and contribution to the distinct physiology of ruminants. The present review summarizes the current understanding of the nature of the BPI-like locus in cattle, including the duplications giving rise to the multiple BSP30 (bovine salivary protein 30?kDa) genes from an ancestral gene in common with the single PSP (parotid secretory protein) gene found in monogastric species. Current knowledge of the expression of the BPI-like proteins in cattle is also presented, including their pattern of expression among tissues, which illustrate their independent regulation at sites of high pathogen exposure, and the abundance of the BSP30 proteins in saliva and salivary tissues. Finally, investigations of the function of the BSP30 proteins are presented, including their antimicrobial, lipopolysaccharide-binding and bacterial aggregation activities. These results are discussed in relation to hypotheses regarding the physiological role of the BPI-like proteins in cattle, including the role they may play in host defence and the unique aspects of digestion in ruminants.     

Phenolics production by encapsulated Nicotiana tabacum cells

Plant cells of tobacco (Nicotiana tabacum L.) were grown for several generations in suspension cultures. Cells were immobilized in continuous bioreactors in calcium alginate (Ca Alg) beads or in poly-L-lysine (PLL) encapsulated calcium alginatehydrogels. In each case, the cells were fed continuously a modified Linsmaier-Skoog plant cell culture medium. The bioreactor effluent was analyzed for total phenolic compounds. The net specific productivity of phenolics was calculated on a daily basis for several test runs. For comparison, productivity in suspension cultures was monitored. Productivity of suspended cells declined to zero within 9 d; both immobilized and encapsulated cells remained productive for 16 d following inoculation. Specific productivity by encapsulated cells was higher than that by immobilized cells; in both types similar rates of decline in productivity occurred.     

Differences between the tolerance characteristics of two anticonvulsant benzodiazepines

Clobazam (10 mg/kg) and clonazepam (0.25 mg/kg) were administered to mice twice daily by the intraperitoneal route. The development of tolerance to their anticonvulsant effect was compared using a slow intravenous infusion of pentylenetetrazole as the convulsant stimulus. Tolerance to clonazepam developed gradually throughout a 72 h study and did not become significant until the fifth dose. In contrast, tolerance to clobazam occurred extremely rapidly, after only one dose; it was manifested as a single step and no further significant change in protection was observed. Recovery from benzodiazepine tolerance was also studied and seen to occur rapidly with both these compounds; following cessation of dosing, protection was restored to initial levels within 36-48 h.     

Evolutionary game auctions

The War of Attrition and the Scotch Auction are instances of a general type of evolutionary game, here referred to as an evolutionary auction. Evolutionary auctions are symmetric, without injury, settled by a single scalar variable (“the bid”), and subject to an overshoot cost function which depends on the difference between the bids. For what appears to be the general class of biologically tenable overshoot cast functions we show that (with the single pathological exception of the Scotch Auction) there is a unique ESS, whose density function is defined on an interval [0, b). Examples are given, and general methods of finding the ESS discussed. Implications for the evolution of animal display behaviour and morphological characters are discussed.